Abstract

2346

Heat shock proteins (hsps) are molecular chaperones which synthesized by cells in response to various stress conditions and associated with tumor neogenesis or carcinogenesis and the biological behaviour of tumors. The expression of hsps in neoplasia has been implicated in the regulation of apoptosis. Recently hsps were emerged to be a novel molecular target in anticancer protocol. The objective of this study was to investigate to clarify the significance of hsp90/70 in breast cancer and effect of geldanamycin (blocker of hsp90) and quercetin (blocker of hsp70) on growth inhibition in different breast cancer cell lines. First, expression levels of hsp 90/70 were studied by immunohistochemistry on tissue sections from 61 invasive ductal carcinoma of breast including 11 ductal carcinoma in situ and 26 normal breast tissues including 12 fibrocystic changes as control. Hsp 70/90 expression were evaluated via grading systems which are percentage-grade is classified by 0(negative),1(25%>),2(25%<),3(50%<),4(75%<) and intensity-grade by 0,1+,2+,3+ according to positive stained cells. Hsps expressions were considered positive if ≥ 50% showed strong reactivity and if ≥ 2+ intensity. Next, we investigated to effect of blocker of hsp90/70 on cell growth of human breast cancer cell lines (MDA-MB 231, MDA-MB 435, MCF-7 and T-47D are all expression of hsp90/70). The effect of geldanamycin(0.1, 1, 10 μM) and quercetin(10, 100, 200 μM) were evaluated via cell growth inhibition assay and apoptosis assay. Hsp 90 showed statistically significant differences between benign and malignant tissue ( p=0.009) but not in hsp 70. Geldanamycin dose dependently and markedly inhibited the cell growth of breast cancer cell lines but quercetin a less inhibited. Therefore, hsp90 may be showed a possibility of an advanced molecular target as adjuvant setting against breast cancer.